This project analyzes neuronal activity in primate frontal lobe to better understand its functional organization. There are three main parts of the frontal lobe in primates: the prefrontal cortex (PF), the premotor cortex (PM) and the primary motor cortex (M1). The former two regions consist of a number of functionally specialized, but functionally related cortical fields. The prevailing theory for the role of PF is that it subserves working memory, with ventral areas being involved in remembering object-related information and dorsolateral regions playing a parallel role for spatial information. However, this theory has recently been shown to be incorrect by researchers in England (Rushworth et al. Journal of Neuroscience 17: 4829-4838, 1997). An alternative theory is that PF is involved in executive functions, a concept which includes generating, evaluating and guiding appropriate actions as well as selecting information relevant to current behavior, in accordance with adaptive behavior-guiding rules (see Wise et al., Critical Reviews in Neurobiology, 10:317-356, 1996). One prediction of the executive function theory is that neuronal activity in PF should reflect behavior-guiding rules in addition to stimulus, response, reward information. We tested that hypothesis to confirm its validity. Approximately half of the PF neurons in the present study showed activity differences that could be attributed to the behavior-guiding rule. Some neurons showed highly selective activity for one rule, some showed selectivity for the other. The proportion of neurons showing rule effects did not vary among the several subdivisions of PF examined, and cells preferring the conditional rule were completely interspersed with those preferring the spatial rule. Selectivity for the stimuli and/or their locations was common. However, there was no regional segregation of such selectivity. These data support the hypothesis that PF plays a role in the guidance of behavior according to previously learned rules and do not support the view that spatial and nonspatial information processing is rigidly segregated within PF. Our data are thus consistent with the theory that PF has an executive role in managing action through the mediation of behavior-guiding rules. We have also tested the hypothesis that the motor areas of frontal cortex show evolving neuronal activity as monkeys become more proficient at learning novel motor skills. The hypothesis that neuronal activity levels significantly change in M1 as monkeys adapt to novel visuomotor transforms was confirmed. A similar proportion is seen in PM as these novel spatial visuomotor transforms are learned. Previous work on this project (Mitz et al., 1991; Chen and Wise, 1995a,b, 1996, 1997) showed that premotor areas have evolving activity as new arbitrary mappings are learned. In spatial transformation learning, visuospatial information is thought to be transformed by the neural network into a motor command signal. Thus, this neural network underlies that analogical mapping of visuospatial inputs to behavior by an algorithmic computation. By contrast, arbitrary mapping involves the use of visual information, which can be spatial and/or nonspatial, to guide movements for which there is no spatial algorithm that relates the visual information to the behavior. Thus, it appears that in addition to the role of PM in mediating arbitrary visuomotor mappings, it has a further role in visuomotor adaptation. These findings suggest that PM is suggests a more general function in visually based selection and guidance of action.